The long-term objectives of this project are to identify genes important for the development and maintenance of the human eye and visual system, to understand their normal actions and interactions, and how these may fail, leading to abnormalities of the visual system. These will be studied in the cave fish model system (Astyanax mexicanus) in which genes causing eye and visual disorders can be mapped and identified. The project has three specific aims: first, we will examine the abnormal eyes of cave/surface hybrids histologically and do QTL mapping in order to better characterize the abnormal phenotypes and understand their genetic bases. This will allow us to recognize similarities to known human eye disorders and increase our knowledge of their causes. Second, we will map genes known to affect eye development or to be expressed in the eye. Some of these genes will prove to be QTL candidates and our analyses will increase our understanding of the ways in which they function in controlling eye development or maintenance. The third aim is to do histological and genetic analyses on the restoration of eye structure and function that occurs in hybrids between two different cave populations. An understanding of the ways in which normal phenotype can be restored by the interaction of elements from two flawed genomes will increase our understanding of the genetic pathways involved in human eye development and disease. [unreadable] [unreadable] [unreadable]